Sickle cell disease is a non-infectious hereditary anemia in which the disease process is well understood at the molecular level: the defective molecule has not only been identified as an abnormal hemoglobin (Hb S), but the abnormal interactions of this molecule can be explained. Observations reported from many laboratories are consistent with an aggregation mechanism due to hydrophobic interactions by deoxy Hb S, as postulated by Murayama. More recently, we have found in our laboratory that both aggregation and solubility of deoxy Hb S are inhibited by inorganic ions in the order of the classical Hofmeister series. We also found that red cells increase in volume upon "sickling." This change, opposite in direction to published claims or predictions, is in the direction of the volume increase during sickling observed by Murayama in his high hydrostatic pressure experiment and with his thermodynamic prediction of the volume of activation. In collaboration with Dr. Oku Ampofo, Dr. J. Obeng, and Dr. M. Appiah in Ghana additional data are obtained supporting our previous finding of the effectiveness of oral carbamide in prevention of crisis and ameliorating the symptoms of sickle cell crises.